An albumin, particularly human serum albumin (hereinafter also referred to as HSA) is an important component constituting protein in plasma. This protein is produced in liver, and is mainly responsible for sustaining normal osmotic pressure of blood flow. Also, it functions as a carrier for various serum molecules. HSA is administered in a variety of clinical situations. For example, when HSA is administered to a patient suffering from shock or ambustion, it functions to recover blood volume to its original level, thereby improving some symptoms relating to trauma. For this effect, HSA is frequently administered. Also, patients suffering from hypoproteinemia or fetal erythroblastosis may need treatments with HSA.
As exemplified, the basic significance of HSA administration is prominent in the treatment of symptoms accompanying loss of fluids from blood vessels, as in surgery, shock, burn, or hypoproteinemia which causes edema.
At present, HSA is produced mainly by fractionation of blood. This production method is uneconomical, and besides, it poses a problem that the supply of the blood is not always assured. Moreover, the blood may contain undesirable substances such as hepatitis viruses. Accordingly, the development of a substitute raw material for HSA will be greatly advantageous.
In the meantime, the advent of the recombinant DNA technique has enabled production of various useful polypeptides by microorganisms, and many mammalian polypeptides have been already produced by various kinds of microorganisms. A technique permitting large-scale production of HSA by utilizing genetic engineering and purification thereof is being established.
Methods for isolating and purifying HSA from plasma have been variously studied and have seen practical application. For example, Cohn's ethanol fractionation, PEG fractionation and ammonium sulfate fractionation are known. In recent years, a combined method of treatment with anion exchanger and heat treatment at 60.degree. C. for 10.hours (Japanese Patent Unexamined Publication No. 191226/1990), and a combined method of treatment with anion exchanger, treatment with cation exchanger and heat treatment at 60.degree. C. for 10 hours (Japanese Patent Unexamined Publication No. 17123/1991) have been developed.
While the purification of recombinant HSA (r-HSA) obtained by genetic engineering has been studied in a variety of ways, the study has not yet succeeded in removing contaminant components derived from yeast. The presence of such component derived from yeast has a probability of causing problems of antigenicity, since the component is a foreign substance to living organisms. That is, the purity of the recombinant type proteins is insufficient and the contaminant component derived from yeast needs to be removed further.